) Preneoplastic cells are generated in human body during their living and working activities. When the control by both host and environmental determinants on the preneoplastic cells is not effective, a tumor will be resulted from the growth of single preneoplastic cell. The effect of surrounding normal cells on preneoplastic cells is a determinant in host, while chemopreventive agent functions as an environmental determinant. The control on tumor growth is affected by the interaction between the two determinants. Chemopreventive agent can show its effect by functioning directly on preneoplastic cells, or indirectly via the control of surrounding normal cells on preneoplastic cells. However, a dose-dependent interfering on surrounding normal cells may also decrease the control effect on preneoplastic cells. To clarify this dual effect of chemopreventive agent on preneoplastic cells is very important before using the chemopreventive agent in humans. This proposed study aims to investigate this interactive effect of chemopreventive agent and surrounding normal cells on the growth and death of preneoplastic cells. (-)-Epigallocatechin gallate (EGCG) in green tea and tea pigments (TP) in black tea are studied, when their cancer chemopreventive effects were reported in cells and animals and also suggested in humans. Three questions will be addressed in this study: a) if EGCG and TP have a dosedependent effect on the clonal growth or death of preneoplastic cells; b) if the effects result from the growth inhibition or killing mechanism directly on preneoplastic cells or indirectly through surrounding normal cells; and c) what are gene expression profile in the cells after regulated by EGCG and TP. A coculture model of normal and transformed Syrian Hamster Embryo (SHE) cells, mimicking in vivo growth environment of preneoplastic cells, will be used to address the questions. Under fluorescence microscopy, the clonal growth and death of single preneoplastic cell can be monitored during study period. The interfering effect between the tea components and normal cells on the growth or death of preneoplastic cells and the mechanism studies on generegulated cell proliferation and apoptosis in preneoplastic cells and surrounding normal cells will put insight in our knowledge about the process of cancer chemoprevention and also tumorigenesis. In addition, the success of this study may also provide a study model for cancer chemopreventive agents.
